What is the cause of hypokalemia (low potassium levels) with metabolic alkalosis and a low anion gap?

From the Guidelines

Hypokalemia with metabolic alkalosis and a low anion gap is often caused by excessive loss of hydrogen and potassium ions, typically due to gastrointestinal or renal causes.

Common Causes

• Gastrointestinal causes:
  • Diarrhea
  • Vomiting
• Renal causes:
  • Diuretic use 1, particularly loop diuretics such as furosemide, which can lead to hypokalemia and metabolic alkalosis
  • Primary hyperaldosteronism
  • Bartter syndrome 1, a rare genetic disorder characterized by hypokalemic metabolic alkalosis

Treatment

Treatment involves addressing the underlying cause, with potassium supplementation using potassium chloride (20-40 mEq/L) administered orally or intravenously, and consideration of spironolactone (25-50 mg daily) or amiloride (5-10 mg daily) to mitigate potassium loss 1.

• In cases of severe hypokalemia, intravenous potassium chloride may be administered at a rate of 10-20 mEq/hour, with close monitoring of serum potassium levels and electrocardiogram findings.
• It is essential to distinguish between renal and gastrointestinal potassium loss and to consider the use of urinary chloride excretion to aid in diagnosis 1.
• Genetic analysis may also be helpful in diagnosing rare tubulopathies such as Bartter syndrome 1.

From the FDA Drug Label

Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of potassium in patients on prolonged parenteral nutrition Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Potassium depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis

• The cause of hypokalemia with metabolic alkalosis and a low anion gap is often due to:
  • Diuretic therapy
  • Primary or secondary hyperaldosteronism
  • Diabetic ketoacidosis
  • Inadequate replacement of potassium in patients on prolonged parenteral nutrition
  • Severe diarrhea, especially if associated with vomiting 2

From the Research

Causes of Hypokalemia with Metabolic Alkalosis and Low Anion Gap

• Hypokalemia is caused by decreased intake, renal losses, gastrointestinal losses, or transcellular shifts 3, 4
• Metabolic alkalosis is characterized by elevated pH and plasma bicarbonate level, and can be caused by gastrointestinal hydrogen and chloride loss, or renal causes 5
• The combination of hypokalemia and metabolic alkalosis can be caused by:
  • Diuretic use, which can lead to renal losses of potassium and chloride, resulting in hypokalemia and metabolic alkalosis 4, 6
  • Gastrointestinal losses, such as vomiting or nasogastric suction, which can lead to loss of hydrogen and chloride ions, resulting in metabolic alkalosis and hypokalemia 5
  • Primary aldosteronism, which can lead to increased renal excretion of potassium and hydrogen ions, resulting in hypokalemia and metabolic alkalosis 6
  • Gitelman syndrome, which can lead to increased renal excretion of potassium, magnesium, and chloride ions, resulting in hypokalemia and metabolic alkalosis 6
• A low anion gap can be seen in cases of metabolic alkalosis caused by gastrointestinal losses or renal causes, as these conditions often result in a loss of chloride ions, which can lead to a decrease in the anion gap 7

Diagnostic Approach

• Measurement of urine chloride concentration can help differentiate between chloride-responsive and chloride-resistant metabolic alkalosis 5, 7
• Urine pH and anion gap can also be useful in diagnosing the cause of metabolic alkalosis, particularly in cases where the history is incomplete or suspicious 7
• Evaluation of effective circulatory volume, renin-angiotensin-aldosterone axis, and measurement of plasma renin activity can also aid in diagnosis 5, 6